BayK 8644 increases resting calcium spark frequency in ferret ventricular myocytes.
BayK 8644, an L-type Ca2+ channel agonist, has been shown to increase sarcoplasmic reticulum (SR) Ca2+ release in dog and ferret ventricular muscle. The visualization of local increase in cytosolic Ca2+ concentration, called the "Ca2+ spark", has enabled us to investigate the elementary events of the BayK-induced Ca2+ release from the SR. In this study, the effects of BayK on twitch Ca2+ transients and Ca2+ sparks were examined in ferret ventricular myocytes with laser scanning confocal microscopy and a fluorescent calcium indicator, fluo 3. BayK converted the post rest potentiation of twitch Ca2+ transients to decay. The Ca2+ spark frequency under control conditions was fairly constant during 20 s of rest after interruption of electrical stimulation. BayK (100 nM) increased the spark frequency by 465.7 +/- 90.3% of control but did not change the spatial and temporal characteristics of the individual sparks. The increase in spark frequency by BayK was not affected by perfusion with Ca(2+)-free solution, but was suppressed by the addition of nifedipine (10 microM), suggesting that the BayK effects on Ca2+ sparks were mediated by the sarcolemmal dihydropyridine (DHP) receptor, but.were independent of Ca2+ influx. These findings suggest that BayK activates SR Ca2+ release at rest through a putative linkage between the sarcolemmal DHP receptor and the SR ryanodine receptor.
Satoh
H
H
Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
Hayashi
H
H
Blatter
L A
LA
Bers
D M
DM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000814:Aniline Compounds; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002478:Cells, Cultured; D004558:Electric Stimulation; D005289:Ferrets; D005456:Fluorescent Dyes; D006352:Heart Ventricles; D018613:Microscopy, Confocal; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014966:Xanthenes
D000814:Aniline Compounds; D002120:Calcium Channel Agonists; D005456:Fluorescent Dyes; D014966:Xanthenes; C059715:Fluo-3; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium